Grand Challenges in Alloimmunity and Transplantation

The pioneering Times Although the concept of Transplantation could be traced back as early as Saint Cosmas and Damian most famous miracle, grafting of a leg to replace a patient’s ulcered leg, it is not before the 50’s that it entered reality. Important steps were made before, from sewing vessels to understanding the basis of the major histocompatibility complex (MHC) in mice (Snell, 1986). This medical field was pioneered in renal transplantation with nearly concomitant attempts in Paris, London, Edinburgh, Boston. The first successful attempt was carried out in Boston by Joseph Murray in 1954. The donor and recipient were identical twins, showing indeed the importance of Genetic compatibility. Organ transplantation (OT) then became one of the most exciting “success story” of modern Medicine, admixing advances in Surgery and intensive care Medicine, Immunology, Genetics, and Pharmacology. The crucial point was first to avoid acute graft rejection which quickly appeared to be immune-mediated. The development of potent immunosuppressive (IS) drugs (corticosteroids, calcineurin inhibitors) opened the way to clinical transplantation. Most critical landmarks were in 1957 the first hepatic transplantation followed by transplantation of other organs, in 1967 the first successful heart transplantation, lung (1968), trachea (1979), pancreas, and more recently hands (2000) and facial tissue (2005). In hematopoietic stem-cell transplantation (HSCT), the initial report of the use of bone marrow transplantation in cancer treatment was made by Thomas in 1957. Several Nobel prizes were awarded to some of the transplantation “founding fathers”: Medawar and Burnet (1960), Benacerraf, Dausset and Snell (1980), Murray and Thomas (1990).